Obesity and its co-morbidities cause about 400,000 deaths and cost $140 billion per year in USA. In veteran patients, obesity is even more prevalent with over 75% of patients overweight or obese. However, currently available therapies are either ineffective or with significant risks o morbidities and mortality. In this project we propose a method of intestinal electrical stimulatio (IES) for treating obesity. Preliminary data have suggested a therapeutic potential of IES for obesity, attributed to its accelerative effect on intestinal transit that leads to reduced absorptin and its effects on peripheral and central hormones/peptides that lead to reduced food intake. To make the IES therapy more potent and practical, we further propose 1) a synchronized IES method (SIES) that has been shown to improve intestinal contractions and is therefore more potent in speeding up intestinal transit; 2) an automatic food intake detection method with which IES/SIES can be delivered automatically upon food ingestion. Our long-term goal is to prove the clinical application of the proposed SIES/IES method for treating obesity. The major objectives of this project are to {optimize IES methodology such that it is most potent in producing weight loss without inducing side-effects, to prove the safety and efficacy of chronic IES/SIES and to explore multiple mechanisms involving gastrointestinal motility and hormones, and central satiety neurons and satiety/appetite-related peptides in diet- induced obese (DIO) rats (a well-established rodent model of human obesity).} {The first series of experiments will be performed in DIO rats to derive best stimulation parameters for IES and best stimulation configuration and best treatment regimen. The second series of experiments are designed to prove that chronic IES/SIES is safe and effective in producing weight loss and improving metabolisms in DIO rats. The third part of the project is to explore multiple mechanisms involved in the inhibitory effect o IES on body weight. Experiments are designed to prove the primary hypothesis that IES reduces body weight by decreasing nutrient absorption via acceleration of intestinal transit. Experiments will also be performed to study the secondary mechanisms associated with satiety signaling, including gastrointestinal hormones, central neuronal responses and central satiety/appetite-related peptides. Advanced technologies will be used for all experiments such that the IES treatment could be given under normal physiological conditions with no or little stress effects. } A comprehensive and competitive team has been assembled with expertise in electrical stimulation, gastrointestinal motility, obesity, surgery, basic laboratory research and statistics. The accomplishment of this project will enhance our understanding on the effects and mechanisms of IES and may lead to a novel therapy for obesity.